The present invention relates to the structural modification of human tissues containing collagen with ultraviolet (UV) irradiation.
Collagen is an insoluble fibrous protein that is present in vertebrates as the chief constituent of connective tissue fibrils, articular cartilage, nucleus pulposus, and in bones. The collagen family represents a diverse group of extracellular matrix molecules that have a triple-helix structure. A single chain of collagen is defined as an xcex1-chain. Each collagen molecule consists of three xcex1-chains usually identical. The only known exception is Type I collagen. Type I collagen consists of two identical chains (xcex11) and one different chain (xcex12). It is the only heteropolymer among collagens. The three polypeptide chains are stabilized as a type II left handed triple helix by intramolecular bonds. The collagen triple helices are processed in the extra-cellular matrix and self-assemble into a fibrillar structure that is stabilized primarily by intermolecular bonds. The triple helix forms a rod-like structure that is important for fibril formation and structural integrity. In higher animals, at least 19 types of collagen have been identified. Type I collagen is the principal component of bone, skin, and tendon, and is the predominant type of collagen in a mature cicatrix (scar). Type II collagen is the major type found in cartilage.
The length and mechanical properties of tissues comprised primarily of type I collagen, such as ligaments, tendons intervertebral discs, and joint capsule, can become altered as a result of an injury or a disease process. Similarly, articular cartilage, comprised primarily of type II collagen, becomes softened in the early stages of osteoarthritis. Recently, thermal energy has been used to shrink lax or redundant tissue containing type I collagen (Hayashi et al. Am. J Sports Med, 1977, 25:107-112). Thermal energy has also been applied to articular cartilage in an attempt to xe2x80x9cstiffenxe2x80x9d damaged surfaces. Infrared (IR) laser energy and radio frequency (RF) energy, either unipolar or bipolar, are presently the two most common delivery systems used in humans for thermal modification of tissues containing collagen (Arnoczky and Aksan, J Am Acad Ortho Surg, 2001, 8:305-313). Thermal energy applied from such heat sources is thought to shrink tissue comprised of collagen by breaking heat-labile intramolecular and intermolecular bonds (such as hydrogen and Van deer Waals bonds), thereby denaturing the collagen from a highly organized pseudo-crystalline structure to a random, gel-like state (Flory and Garret, J Am Chem Soc, 1958, 80:4836-4845). Furthermore, unlike some other proteins, heat denatured collagen is unable to refold back to its organized structure.
However, while thermal denaturization shrinks tissue containing collagen, it also decreases the elastic modulus (modulus) of the treated tissue. Wall and co-workers demonstrated that for thermal denaturization of bovine extensor tendon, comprised primarily of type I collagen, shrinkage of the tissue is both temperature and time dependent (see FIG. 1) (Wall et al. J Shoulder Elbow Surg, 1999, 8:339-344). But, as illustrated graphically in FIG. 2, the modulus of thermally denatured tissue decreases as a function of the percent of tissue shrinkage.
Although the theory relating to such loss of modulus after thermal treatment is not fully understood, the mechanism of thermal denaturization of collagen might be partially understood by referring to its molecular structure (Brodsky and Ramshaw, Matrix Bio, 1997, 15:545-554). The application of thermal energy to collagen disrupts heat labile bonds (e.g. hydrogen bonds between the xcex1 chains) and causes the collagen triple helix to unwind, leaving the polypeptide chains in a denatured state.
Weakening of thermally denatured tissues containing collagen presents a serious clinical problem for patients in the immediate post-operative period. More specifically, tissue that has been shortened or smoothed by thermal denaturization is at risk to stretch out with any applied tensile force. Therefore, there is a continuing need in the art to develop methods to treat tissues that are too lax or too tight.
Thus it is an object of the present invention to provide a method for modifying tissue modulus of elasticity.
It is a further object of the present invention to provide an apparatus for modifying the mechanical properties of tissue.
It is still a further object of the present invention to provide an apparatus and a method for modifying tissue modulus of elasticity while maintaining the positive molecular and mechanical characteristics of non-thermally denatured tissues.
The foregoing objects and advantages of the invention are illustrative of those that can be achieved by the present invention and are not intended to be exhaustive or limiting of the possible advantages which can be realized. Thus, these and other objects and advantages of the invention will be apparent from the description herein or can be learned from practicing the invention, both as embodied herein or as modified in view of any variation which may be apparent to those skilled in the art. Accordingly, the present invention resides in the novel methods, arrangements, combinations and improvements herein shown and described.
In light of the present need for providing an efficient and reliable apparatus for performing a method for modifying tissue modulus of elasticity, a brief summary of the present invention is presented. Some simplifications and omission may be made in the following summary, which is intended to highlight and introduce some aspects of the present invention, but not to limit its scope. Detailed descriptions of a preferred exemplary embodiment adequate to allow those of ordinary skill in the art to make and use the invention concepts will follow in later sections.
The present invention contemplates a method for modifying tissue modulus of elasticity, where the method comprises the steps of (a) maintaining the temperature of the tissue within a selected temperature range, (b) providing UV photons at a predetermine wavelength or within a selected wavelength range, and (c) irradiating the tissue with a selected dose of UV photons at a predetermined intensity for a predetermined length of time. In one embodiment of the present invention, the method further comprises maintaining the pH of the tissue and/or adding at least one pharmaceutically acceptable free radical producing compound. In a further embodiment of the present invention, the method further comprises testing the tissues prior to the method. The steps of the present method may be performed in any order to produce the desired results. In a further embodiment of the present invention, the selected temperature may be either above the temperature required for denaturization of collagen within the tissue (e.g., from about 55 degrees C. to about 65 degrees C.) or below the temperature range required for denaturization of collagen within the tissue (e.g., from about 37 degrees C. to about 39 degrees C.). The UV photons may be delivered through a fiber optic cable. The present invention may be used on any tissues, such as joint capsule, tendon, ligament, fibrocartilage, hyaline cartilage, bone, skin and muscle. The wavelengths that may be used are preferably 250 nm-420 nm, more preferably 320 nm-390 nm.
The present invention also contemplates an apparatus for modifying mechanical properties of tissue. The apparatus may be comprised of a means for maintaining the temperature of the tissue, a means for generating UV photons at a selected wavelength and intensity; a means for irradiating the tissue with the UV photons; and a means for controlling the wavelength, the intensity, and the temperature. The present apparatus may further comprise a means for measuring the thickness and stiffness of the tissue.
The present invention also contemplates a method for increasing modulus of elasticity in a patient in need thereof, where the method comprises administering the method of the invention.